In no other field of medicine is the therapeutic risk higher than in the treatment of pregnant women. While in the adult most of the unexpected side effects of drugs are reversible, they are irreversible in the embryo and developing fetus and can lead to abnormalities in the newborn. We propose to continue our studies of drugs of abuse and maternal-fetal pharmacology. The animal model to be utilized in these studies is the nonhuman primate, Macaca arctoides. Studies will focus on (1) the pharmacokinetics of drugs of abuse in the pregnant and nonpregnant monkey and (2) the development of fetal hepatic drug metabolism. Drugs to be studied with respect to pharmacokinetics in pregnant monkeys include, but are not limited to, barbiturates, methadone, meperidine, and LAAM. The in vitro metabolism of these drugs in whole homogenates of the separate lobes of fetal liver as well as by microsomes isolated from fetal liver at various gestational ages will also be studied. This investigation into the problem of drugs of abuse and the pregnant patient and the effect of such drugs on fetal hepatic metabolism should supply information upon which to develop rational, safe, and effective utilization of therapeutic agents in the pregnant patient.